The Link Between Diabetes Risk and Polyunsaturated Fatty Acids

Higher consumption of linoleic acid and higher levels in the body may mitigate diabetes mellitus risk.

The primary polyunsaturated fatty acid (PUFA) is linoleic acid (LA), an essential fatty acid that makes up 85 to 90% of PUFA dietary consumption in the US. PUFA’s are classified into n-9, n-6, and n-3 fats. It is generally obtained from nuts and plant oils and recommended by dietary guidelines for health purposes such as the American Heart Association (AHA) and the Dietary Guidelines for Americans. They recommend the intake of 5 to 10% of total calories of LA. The health advantages of LA exhibited from previous studies show a total reduction in LDL, VLDL, triglycerides, and increased HDL levels. Randomized control trials (RCT) showed PUFA consumption, mainly LA, improved blood glucose and insulin resistance. Prospective cohort studies revealed an inverse association between dietary LA consumption, biomarkers, and stroke and coronary heart disease (CHD) risk. Furthermore, greater dietary LA consumption correlated with a reduced risk of all-cause and cancer mortality. Despite the found benefits of LA, some experts believe it may cause adverse health effects since LA is a precursor arachidonic acid. Diet LA consumption, including biomarkers and type 2 diabetes (T2D) frequency, is still debatable. The following meta-analysis is the initial review of dietary LA consumption and its biomarkers concerning T2D occurrence.

Past meta-analyses were centralized on the correlation between PUFA and cardiovascular disease endpoints, and less have concentrated on diabetes risk. The purpose of the current review by Schulze et al. was to quantify the summary of results reported from prospective cohort studies concerning the connection of the risk of T2D and dietary LA consumption and its biomarkers in the total population. Studies were included in the assessment if they were prospective cohort, observational, nested case-control, or case-cohort studies. In addition, studies were performed in the general public aged ≥18 years, and studies that used multivariable-adjusted risk assessments of the correlation between LA (exposure) and T2D (outcome) were also included. The meta-analysis did not include populations with chronic health problems, pregnant women, children, and adolescents. Altogether, 31 cohorts were included, consisting of 297,685 individuals (22,639 were cases of T2D incidents) with dietary intake evaluation and biomarker assessments in 84,171 individuals (18,458 were cases of T2D incidents). The inverse variant method was used to calculate the relative risk (RR) of LA consumption and biomarkers. Restricted cubic splines were used to model dose-response associations.

The current review and meta-analysis of the prospective cohort studies observed an inverse correlation between the risk of T2D and dietary consumption of LA and its biomarkers. Higher consumption of LA was reported as a 6% reduced risk of T2D. In the dose-response analysis, the magnitude of the relationship demonstrated that every 5% increase in energy from LA consumption was linked with a risk reduction of T2D by 10% and a 15% reduction of T2D risk increase per SD in LA biomarker levels. A nonlinear correlation between LA consumption and T2D was noted, with the highest consumption at the lowest risks. The correlation with LA biomarkers was strong but not necessarily with LA intake due to the individual exclusion of studies, leading to the inconsequential association of dietary LA. The RR for diabetes per SD increase in LA levels in adipose tissue or blood compartments was 0.85. Multiple strengths were identified in this review including, an ample number of prospective cohorts from Asia, Europe, and the US, making it highly generalizable. Moreover, ample patients and cases lead to increased statistical power to identify an association of high importance. Performing linear and nonlinear dose-response analyses were used to elucidate the shape and strength of the detected correlations. Sensitivity analyses were not changed regarding the correlation between LA biomarker levels and T2D risk, indicating results were strong. The review considered all compartments for LA biomarker levels; however, only a single study identified LA in the adipose tissue, the benchmark for reflecting dietary fatty acids; further examination is warranted for LA adipose tissue and T2D risk. Measurement errors may have influenced the dose-response curve, different methods were used to identify T2D, and the final data of dietary LA consumption was not significant, to name a few. Additional studies are vital to make a concrete conclusion concerning the correlation between dietary LA consumption and the risk of T2D.

Practical Pearls

• High consumption of dietary LA and high LA concentrations in the body had a significant relation to decreased risk of T2D.
• An inverse correlation between the risk of T2D and dietary consumption of LA and its biomarkers was observed.
• The connection between LA and lowered diabetes risk was considerable at a consumption of 5.5–7.0% of energy from LA.

Schulze, Matthias B. “Dietary Linoleic Acid: Will Modifying Dietary Fat Quality Reduce the Risk of Type 2 Diabetes?.” Diabetes care vol. 44,9 (2021): 1913-1915. doi:10.2337/dci21-0031.

https://care.diabetesjournals.org/content/diacare/44/9/1913.full.pdf

Mousavi, Seyed Mohammad et al. “Dietary Intake of Linoleic Acid, Its Concentrations, and the Risk of Type 2 Diabetes: A Systematic Review and Dose-Response Meta-analysis of Prospective Cohort Studies.” Diabetes care vol. 44,9 (2021): 2173-2181. doi:10.2337/dc21-0438. https://care.diabetesjournals.org/content/44/9/2173.long

Mensink, Ronald P et al. “Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials.” The American journal of clinical nutrition vol. 77,5 (2003): 1146-55. doi:10.1093/ajcn/77.5.1146. https://academic-oup-com.proxy.hsl.ucdenver.edu/ajcn/article/77/5/1146/4689813

Russo, Gian Luigi. “Dietary n-6 and n-3 polyunsaturated fatty acids: from biochemistry to clinical implications in cardiovascular prevention.” Biochemical pharmacology vol. 77,6 (2009): 937-46. doi:10.1016/j.bcp.2008.10.020. https://www-sciencedirect-com.proxy.hsl.ucdenver.edu/science/article/pii/S0006295208007776

Trina Maglalang RPh, 2022 PharmD Candidate University of Colorado